(f) Methyl 2-fluoro-4-methylbenzoate (5): Method A: To a mixture of 2-fluoro-4-methylbenzoic acid (2.0 g, 13.0 mmol) and K2CO3 (3.6 g, 26.0 mmol) in acetonitrile (15 mL) was added CH3I (1.6 mL, 25.6 mmol) dropwise with stirring. The reaction mixture was heated to reflux overnight and the solvent was removed by distillation under reduced pressure. The residue was dissolved with EtOAc, washed sequentially with water and saturated saline, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with hexane/EtOAc (6:1) as eluent to give a white solid 5 (1.73 g, 79% yield) with melting point 51-53 °C.1H NMR (CDCl3) δ: 7.83 (t, J=8.0 Hz, 1H), 7.00 (dd, J=8.0,1.0 Hz, 1H), 6.95 (d, J= 12.0 Hz, 1H), 3.91 (s, 3H), 2.39 (s, 3H). Method B: Concentrated sulfuric acid (5 mL) was added dropwise to a solution of 2-fluoro-4-methylbenzoic acid (7.0 g, 45.4 mmol) in MeOH (100 mL) under stirring. The reaction mixture was heated to reflux overnight and then the solvent was removed by distillation under reduced pressure. The residue was dissolved with EtOAc, washed with saturated aqueous NaHCO3 and saturated saline in turn, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with hexane/EtOAc (6:1) as eluent to give white solid 5 (6.88 g, 90% yield). The analytical data were the same as that of Method A.
